Dataset Information

Improving protein function prediction using protein sequence and GO-term similarities.

ABSTRACT: MOTIVATION:Most automatic functional annotation methods assign Gene Ontology (GO) terms to proteins based on annotations of highly similar proteins. We advocate that proteins that are less similar are still informative. Also, despite their simplicity and structure, GO terms seem to be hard for computers to learn, in particular the Biological Process ontology, which has the most terms (>29 000). We propose to use Label-Space Dimensionality Reduction (LSDR) techniques to exploit the redundancy of GO terms and transform them into a more compact latent representation that is easier to predict. RESULTS:We compare proteins using a sequence similarity profile (SSP) to a set of annotated training proteins. We introduce two new LSDR methods, one based on the structure of the GO, and one based on semantic similarity of terms. We show that these LSDR methods, as well as three existing ones, improve the Critical Assessment of Functional Annotation performance of several function prediction algorithms. Cross-validation experiments on Arabidopsis thaliana proteins pinpoint the superiority of our GO-aware LSDR over generic LSDR. Our experiments on A.thaliana proteins show that the SSP representation in combination with a kNN classifier outperforms state-of-the-art and baseline methods in terms of cross-validated F-measure. AVAILABILITY AND IMPLEMENTATION:Source code for the experiments is available at https://github.com/stamakro/SSP-LSDR. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

SUBMITTER: Makrodimitris S

PROVIDER: S-EPMC6449755 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Improving protein function prediction using protein sequence and GO-term similarities.

Makrodimitris Stavros S van Ham Roeland C H J RCHJ Reinders Marcel J T MJT

Bioinformatics (Oxford, England) 20190401 7

<h4>Motivation</h4>Most automatic functional annotation methods assign Gene Ontology (GO) terms to proteins based on annotations of highly similar proteins. We advocate that proteins that are less similar are still informative. Also, despite their simplicity and structure, GO terms seem to be hard for computers to learn, in particular the Biological Process ontology, which has the most terms (>29 000). We propose to use Label-Space Dimensionality Reduction (LSDR) techniques to exploit the redund ...[more]

PMID: 30169569

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Project description:MotivationProtein structure prediction has been greatly improved by deep learning, but the contribution of different information is yet to be fully understood. This article studies the impacts of two kinds of information for structure prediction: template and multiple sequence alignment (MSA) embedding. Templates have been used by some methods before, such as AlphaFold2, RoseTTAFold and RaptorX. AlphaFold2 and RosetTTAFold only used templates detected by HHsearch, which may not perform very well on some targets. In addition, sequence embedding generated by pre-trained protein language models has not been fully explored for structure prediction. In this article, we study the impact of templates (including the number of templates, the template quality and how the templates are generated) on protein structure prediction accuracy, especially when the templates are detected by methods other than HHsearch. We also study the impact of sequence embedding (generated by MSATransformer and ESM-1b) on structure prediction.ResultsWe have implemented a deep learning method for protein structure prediction that may take templates and MSA embedding as extra inputs. We study the contribution of templates and MSA embedding to structure prediction accuracy. Our experimental results show that templates can improve structure prediction on 71 of 110 CASP13 (13th Critical Assessment of Structure Prediction) targets and 47 of 91 CASP14 targets, and templates are particularly useful for targets with similar templates. MSA embedding can improve structure prediction on 63 of 91 CASP14 (14th Critical Assessment of Structure Prediction) targets and 87 of 183 CAMEO targets and is particularly useful for proteins with shallow MSAs. When both templates and MSA embedding are used, our method can predict correct folds (TMscore > 0.5) for 16 of 23 CASP14 FM targets and 14 of 18 Continuous Automated Model Evaluation (CAMEO) targets, outperforming RoseTTAFold by 5% and 7%, respectively.Availability and implementationAvailable at https://github.com/xluo233/RaptorXFold.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:BackgroundDetermining the function of uncharacterized proteins is a major challenge in the post-genomic era due to the problem's complexity and scale. Identifying a protein's function contributes to an understanding of its role in the involved pathways, its suitability as a drug target, and its potential for protein modifications. Several graph-theoretic approaches predict unidentified functions of proteins by using the functional annotations of better-characterized proteins in protein-protein interaction networks. We systematically consider the use of literature co-occurrence data, introduce a new method for quantifying the reliability of co-occurrence and test how performance differs across species. We also quantify changes in performance as the prediction algorithms annotate with increased specificity.ResultsWe find that including information on the co-occurrence of proteins within an abstract greatly boosts performance in the Functional Flow graph-theoretic function prediction algorithm in yeast, fly and worm. This increase in performance is not simply due to the presence of additional edges since supplementing protein-protein interactions with co-occurrence data outperforms supplementing with a comparably-sized genetic interaction dataset. Through the combination of protein-protein interactions and co-occurrence data, the neighborhood around unknown proteins is quickly connected to well-characterized nodes which global prediction algorithms can exploit. Our method for quantifying co-occurrence reliability shows superior performance to the other methods, particularly at threshold values around 10% which yield the best trade off between coverage and accuracy. In contrast, the traditional way of asserting co-occurrence when at least one abstract mentions both proteins proves to be the worst method for generating co-occurrence data, introducing too many false positives. Annotating the functions with greater specificity is harder, but co-occurrence data still proves beneficial.ConclusionCo-occurrence data is a valuable supplemental source for graph-theoretic function prediction algorithms. A rapidly growing literature corpus ensures that co-occurrence data is a readily-available resource for nearly every studied organism, particularly those with small protein interaction databases. Though arguably biased toward known genes, co-occurrence data provides critical additional links to well-studied regions in the interaction network that graph-theoretic function prediction algorithms can exploit.

Dataset Information

Improving protein function prediction using protein sequence and GO-term similarities.

Publications

Improving protein function prediction using protein sequence and GO-term similarities.

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